Reversal of profound rocuronium-induced blockade with sugammadex: a randomized comparison with neostigmine.
BACKGROUND
Traditionally, reversal of nondepolarizing neuromuscular blocking agents was achieved using acetylcholinesterase inhibitors, but these are unable to adequately reverse profound blockade. Sugammadex is a novel reversal agent, reversing the effects of rocuronium by encapsulation. This study assessed the efficacy and safety of sugammadex versus neostigmine for reversal of profound rocuronium-induced neuromuscular blockade.


METHODS
This phase III, randomized study enrolled surgical patients, aged 18 yr or older with American Society of Anesthesiologists physical status I-IV. Patients were randomized to receive sugammadex (4.0 mg/kg) or neostigmine (70 microg/kg) plus glycopyrrolate (14 microg/kg). Anesthetized patients received an intubating dose of rocuronium (0.6 mg/kg), with maintenance doses (0.15 mg/kg) as required. Neuromuscular monitoring was performed by acceleromyography. Sugammadex or neostigmine was administered at reappearance of 1-2 posttetanic counts (profound neuromuscular blockade). The primary efficacy parameter was the time from sugammadex or neostigmine-glycopyrrolate administration to return of the train-of-four ratio to 0.9.


RESULTS
In the intent-to-treat population (n = 37 in each group), geometric mean time to recovery to a train-of-four ratio of 0.9 with sugammadex was 2.9 min versus 50.4 min with neostigmine-glycopyrrolate (P < 0.0001) (median, 2.7 min vs. 49.0 min). Most sugammadex patients (97%) recovered to a train-of-four ratio of 0.9 within 5 min after administration. In contrast, most neostigmine patients (73%) recovered between 30 and 60 min after administration, with 23% requiring more than 60 min to recover to a train-of-four ratio of 0.9.


CONCLUSIONS
Recovery from profound rocuronium-induced neuromuscular blockade was significantly faster with sugammadex versus with neostigmine, suggesting that sugammadex has a unique ability to rapidly reverse profound rocuronium neuromuscular blockade.
Jones
R Kevin
RK
Accurate Clinical Trials/Saddleback Memorial Medical Center, Laguna Hills, CA 92653, USA. kevinjones@accurateclinicaltrials.net
Caldwell
James E
JE
Brull
Sorin J
SJ
Soto
Roy G
RG
D000328:Adult; D000368:Aged; D000732:Androstanols / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009388:Neostigmine / Q000494:pharmacology*; D019148:Neuromuscular Blockade / Q000379:methods*; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology; D003473:Neuromuscular Nondepolarizing Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000077123:Rocuronium; D016037:Single-Blind Method; D000077122:Sugammadex; D047408:gamma-Cyclodextrins / Q000494:pharmacology*
D000732:Androstanols; D003473:Neuromuscular Nondepolarizing Agents; D047408:gamma-Cyclodextrins; D000077122:Sugammadex; D009388:Neostigmine; D000077123:Rocuronium